Mother's recorded voice on emergence can decrease postoperative emergence delirium from general anaesthesia in paediatric patients: a prospective randomised controlled trial.

BACKGROUND: Emergence delirium is a behavioural disturbance after general anaesthesia in children that can distress patients, parents, and primary caregivers. We hypothesised that listening to the mother's recorded voice can reduce ED compared with listening to a stranger's recorded voice. METHODS: This prospective, double-blind, randomised study was conducted in 2- to 8-yr-old patients who had undergone general anaesthesia. Sixty-six patients were randomly assigned to listen to either the mother's voice (Group M, n=33) or a stranger's voice (Group S, n=33). The primary outcome was the initial paediatric assessment of emergence delirium (PAED) score on arrival at a postanaesthesia care unit (PACU). Other outcomes were the incidence of emergence delirium; Watcha, PAED, and pain scores; PACU stay time; durations between cessation of anaesthetics and bispectral index (BIS) levels of 60, 70, and 80; eye opening time; extubation time; and total consumption of analgesics during the PACU stay. RESULTS: The mother's voice reduced the initial PAED score compared with a stranger's voice [mean (standard deviation), 9.8 (2.5) vs 12.5 (4.1); P=0.002]. The incidence of emergence delirium during the PACU stay was higher in Group S than in Group M [60.6% vs 24.2%, odds ratio (95% confidence interval): 4.88 (1.7-13.9); P=0.006]. The BIS >60 time was shorter in Group M than in Group S (P=0.006). CONCLUSIONS: The mother's voice reduced emergence delirium scores and the incidence of emergence delirium in paediatric patients compared with a stranger's voice after general anaesthesia. CLINICAL TRIAL REGISTRATION: NCT 02955680.

Peptidylarginine deiminase is involved in maintaining the cornified oral mucosa of rats.

BACKGROUND AND OBJECTIVE: Epithelial cells derived from different regions exhibit marked differences in their differentiation capacity, allowing them to provide a suitable protective barrier. We aimed to clarify the role of peptidylarginine deiminase (PAD) in modifying the key epidermal proteins filaggrin (FLG) and keratin 1 (K1) during stratification of the rat palate and buccal mucosa. MATERIAL AND METHODS: We performed immunofluorescence, immunoblotting, PAD activity assays and 2-dimensional electrophoresis, and developed an organotypic culture model. RESULTS: PAD1 expression was highest in the palate, whereas PAD2, PAD3 and PAD4 expression was highest in the skin, suggesting the tissue-specific expression of PAD isozymes that leads to differences in calcium dependency. Immunoblotting showed that the FLG monomer, as well as its degradation products and precursor (proFLG), were most abundantly expressed in the skin but had low expression in the palate, whereas only faint proFLG expression was detected in the buccal mucosa. FLG and K1 were colocalized with PAD1 and were likely to be citrullinated in the cornified layers of the skin; this colocalization was not detected on the palatal surface, and dot-like presence of proFLG that might be citrullinated and that of PAD1 were found in the granules of the palate. Organotypic models derived from the rat palate revealed that PAD inhibition reduced the breakdown of FLG, increased its association with K1 together with epithelial compaction, and decreased permeability in a dye permeability assay. Conversely, PAD stimulation had the opposite effects. CONCLUSION: Citrullination is likely a protein modification that plays an important role in maintaining the structure and function of oral cornified mucosa in a way that is distinctly different from that of the skin.

Genomes of coral dinoflagellate symbionts highlight evolutionary adaptations conducive to a symbiotic lifestyle.

Despite half a century of research, the biology of dinoflagellates remains enigmatic: they defy many functional and genetic traits attributed to typical eukaryotic cells. Genomic approaches to study dinoflagellates are often stymied due to their large, multi-gigabase genomes. Members of the genus Symbiodinium are photosynthetic endosymbionts of stony corals that provide the foundation of coral reef ecosystems. Their smaller genome sizes provide an opportunity to interrogate evolution and functionality of dinoflagellate genomes and endosymbiosis. We sequenced the genome of the ancestral Symbiodinium microadriaticum and compared it to the genomes of the more derived Symbiodinium minutum and Symbiodinium kawagutii and eukaryote model systems as well as transcriptomes from other dinoflagellates. Comparative analyses of genome and transcriptome protein sets show that all dinoflagellates, not only Symbiodinium, possess significantly more transmembrane transporters involved in the exchange of amino acids, lipids, and glycerol than other eukaryotes. Importantly, we find that only Symbiodinium harbor an extensive transporter repertoire associated with the provisioning of carbon and nitrogen. Analyses of these transporters show species-specific expansions, which provides a genomic basis to explain differential compatibilities to an array of hosts and environments, and highlights the putative importance of gene duplications as an evolutionary mechanism in dinoflagellates and Symbiodinium.

Effects of Allopurinol and Apocynin on Renal Ischemia-Reperfusion Injury in Rats.

BACKGROUND: This study evaluated the effects of allopurinol (ALP), a xanthine oxidase inhibitor, and apocynin (APC), a NADPH oxidase inhibitor, administered alone or together, on kidney damage caused by renal ischemia-reperfusion (IR) in rats. METHODS: Thirty rats were randomly assigned to 5 groups. Group 1 was a sham group. Group 2 was the renal IR control group (30-min ischemia followed by 24-h reperfusion). In groups 3 and 4, ALP or APC, respectively, was administered 1 h before the ischemia. In group 5, ALP and APC were co-administered. Blood urea nitrogen (BUN) and serum creatinine (Cr), renal tissue malondialdehyde (MDA) and superoxide dismutase (SOD), and histological changes were evaluated. RESULTS: A significant increase in BUN and Cr level, and histological damage was seen in the IR control group, indicating renal injury. Elevated MDA and decreased SOD levels in the IR control group demonstrated that renal damage occurred through oxidative stress. Pretreatment with ALP or APC alone or together prevented IR-induced renal damage. However, there was no significant difference between treatment with a single drug and co-administration of ALP and APC. CONCLUSIONS: The use of ALP and/or APC before ischemia may be beneficial to ameliorate renal IR injury.

Optimal central venous pressure during the neohepatic phase to decrease peak portal vein flow velocity for the prevention of portal hyperperfusion in patients undergoing living donor liver transplantation.

BACKGROUND: The association between intraoperative systemic hemodynamic status and preventing portal hyperperfusion, which induces shear stress on the sinusoidal endothelial cells of liver grafts, resulting in poor graft function in live-donor recipients, has not been identified. This study evaluates the effects of systemic hemodynamic parameters (SHPs) during the neohepatic phase on changes in hepatic hemodynamic parameters (HHPs) between the neohepatic phase and the 1st postoperative day. METHODS: Thirty-eight patients undergoing living donor liver transplantation (LDLT) were enrolled in this study. HHPs (flow velocities of portal vein and hepatic artery) were measured immediately after hepatic artery and bile duct reconstruction and on the first postoperative day. SHPs (mean arterial pressure, central venous pressure [CVP], cardiac index, stroke volume variation, stroke volume index, systemic vascular resistance index, and central venous oxygen saturation) were recorded and averaged for 5 minutes after the measurement of HHPs. The relationships between the SHPs and HHPs were assessed using linear or quadratic regression analysis. RESULTS: Peak portal vein flow velocity (PVV) decreased on the 1st postoperative day in 24 patients (63%). There was an inverted-U relationship between CVP and the percentage change in PVV (R(2) = 0.241, P = .008). According to the quadratic regression model, the PVV maximally decreased at a CVP of 7.8 mm Hg. No significant correlations were found between the other SHPs and HHPs. CONCLUSIONS: Maintaining CVP (approximately 8 mm Hg) during the neohepatic phase was clinically beneficial in decreasing PVV to prevent portal hyperperfusion in the early postoperative period of LDLT.

Transplantation of newborn thymus plus hematopoietic stem cells can rescue supralethally irradiated mice.

We attempted to rescue supralethally irradiated (SLI) mice by transplantation of hematopoietic stem cells (HSCs) plus thymus from variously aged donors (fetus, newborn and adult). Although the transplantations of these kinds of HSCs alone showed a very short survival, newborn liver cells (NLCs) (as the source of HSCs) plus newborn thymus (NT) transplantation markedly improved the survival rate. The transplantation attenuated severe damage in the small intestine, which is one of the major causes of death by SLI. In addition, the donor-derived CD4(+) T cells significantly increased with additional NT transplantation. The production of interleukin (IL)-7 and keratinocyte growth factor, which plays a crucial role in protection against radiation injury in the intestine, was the highest in NT. Finally, SLI mice that had received NLC plus IL-7(-/-) NT transplantation plus IL-7 injection showed improved survival, weight recovery and an elevated number of CD4(+) T cells compared with the mice that had received NLC plus IL-7(-/-) NT or plus IL-7 injection alone. These findings suggest that NLCs plus NT transplantation can rescue SLI mice most effectively, and that high production of IL-7 in NT plays a crucial role with induction of CD4(+) T cells.

Treatment of autoimmune diseases in MRL/lpr mice by allogenic bone marrow transplantation plus adult thymus transplantation.

MRL/lpr mice (H-2(k)) with Fas gene mutation develop severe autoimmune diseases, and their haematolymphoid cells such as bone marrow and spleen cells showed a low apoptotic activity by irradiation. Therefore, conventional bone marrow transplantation (BMT) cannot be used to treat autoimmune diseases in these mice (chimeric resistance). In the present study, we examine the effects of additional adult thymus transplantation (TT) from the same donor on successful BMT. When the MRL/lpr mice were lethally irradiated (9 x 5Gy) and reconstituted with 3 x 10(7) of C57BL/6 mouse (H-2b) bone marrow cells (BMCs) in conjunction with TT, the mice significantly survived long term and showed a high donor-derived chimerism in comparison with those treated with BMT alone. Interestingly, the numbers of not only donor-derived T cells but also B cells increased significantly in the mice treated with BMT plus TT, even at the early phase of BMT. The number of aberrant CD3+B220+ cells decreased significantly, and the numbers of lymphocyte subsets were also normalized 4 weeks after the treatment. Finally, the autoimmune diseases in MRL/lpr mice could be cured by BMT with TT. These results indicate that the combination of BMT plus TT can overcome the chimeric resistance and treat the autoimmune diseases in MRL/lpr mice.

Relationship of p53, Bcl-2, Ki-67 index and E-cadherin expression in early invasive breast cancers with comedonecrosis as an accelerated apoptosis.

AIMS: To study the relationship between comedonecrosis formation and morphology, apoptosis, and p53, Bcl-2, Ki-67 index and E-cadherin expression in early invasive breast cancer. EXPERIMENTAL DESIGN: Early invasive breast cancers were first divided into two groups according to the presence (CN+ tumours) or absence (CN- tumours) of comedonecrosis. The histological grade, apoptosis, and expression of E-cadherin, Ki-67, p53 and Bcl-2 in the cancer-affected area, and in normal ducts from the specimen, were then examined. RESULTS: Less tubule and gland formation was seen in CN+ tumours than in CN- tumours, although the histological grade between the groups was not different. During early comedonecrosis, cells undergo apoptosis and subsequent necrosis. p53 was higher in CN+ tumours than in CN- tumours and normal ducts, whereas Bcl-2 was lower in CN+ tumours than in CN- tumours and normal ducts. Both tumours had higher Ki-67 than in normal ducts, but no difference was evident between the tumours. CN+ tumours had slightly higher E-cadherin than that in CN- tumours, but lower than that in normal ducts. The level of comedonecrosis was positively correlated with p53, but inversely correlated with Bcl-2 in all tumours, and p53 and Bcl-2 were inversely correlated with each other. Furthermore, comedonecrosis and p53 were correlated with Ki-67 in CN+ tumours, and Bcl-2 was correlated with Ki-67 in CN- tumours. CONCLUSION: Comedonecrosis may be actively regulated through an apoptotic procedure in massive cancers for their survival and progression, and the above proteins may be associated cooperatively in this process. CN+ and CN- tumours may have opposite proliferative systems under the p53-Bcl-2 pathway.

Rapidly progressive tabes dorsalis associated with selective IgA deficiency.

Tabes dorsalis is uncommon and progresses slowly from infection to clinical manifestation. We report a rare case of rapidly progressive tabes dorsalis associated with selective IgA deficiency (sIgAD). A 28-year-old man was hospitalized with lightning back pain, nausea, and bladder bowel dysfunction. Serum and cerebrospinal fluid (CSF) revealed high titers of Treponema pallidum antibody, and the serum IgA level was less than 5 mg/dl. Thl-dominant cytokine expression was observed, as is usually seen in neurosyphilis. He was treated with Ceftriaxone and CSF pleocytosis disappeared. We postulate sIgAD influenced the atypical rapid clinical course of tabes dorsalis in this patient.

Relapsing polychondritis: a report of eight cases.

OBJECTIVE: To investigate clinical manifestations of relapsing polychondritis and to clarify the significance of type II collagen antibody in the disease. METHODS: Clinical manifestations and antibody titers were examined in eight cases of relapsing polychondritis which had been treated at Otolaryngology Department, Hokkaido University during the eight years from 1991 to 1998. Anti-type II collagen antibody titer was measured by ELISA method. RESULTS: The most frequent symptom was auricular chondritis; it was seen in 88% (7/8) of the cases. Ocular symptom, nasal chondritis, arthritis, respiratory tract chondritis, and audio-vestibular symptom were also common in the cases. Compared with previous reports, no difference was recognized in the manifestation frequency. Considering none of the samples from the controls was positive for anti-type II collagen antibody, two samples from the disease group were positive. The antibody positive rate was 25% (2/8). CONCLUSION: Though the measurement of type II collagen antibody titer is not a decisive factor for detection of relapsing polychondritis, it is useful as one of the complementary factors for the diagnosis, since there is no specific test for this disease.

Myelodysplasia associated with acquired immunodeficiency syndrome.

Two cases of acquired immunodeficiency syndrome with myelodysplasia are presented. Case 1 was admitted because of Pneumocystis carinii pneumonia. Mild anemia, thrombocytopenia and hypersegmented neutrophils were observed. After the administration of trimethoprim-sulfame-thoxazole and antiretroviral therapy, pancytopenia progressed. Bone marrow (BM) showed dysplastic hematopoiesis, suggesting human immunodeficiency virus-myelopathy. Case 2 was hospitalized due to progressive multifocal leukoencephalopathy. BM specimen obtained for thrombocytopenia showed myelodysplasia similar to myelodysplastic syndrome, suggesting that HIV may have an influence on hematopoietic progenitor cells.

Conjugation with L-Glutamate for in vivo brain drug delivery.

In vitro studies have shown that conjugation of a model compound [p-di(hydroxyethyl)-amino-D-phenylalanine (D-MOD)] with L-Glu can improve D-MOD permeation through the bovine brain microvessel endothelial cell monolayers (Sakaeda et al., 2000). The transport of this D-MOD-L-Glu conjugate is facilitated by the L-Glu transport system. In this paper, we evaluate the in vivo brain delivery of model compounds (i.e. D-MOD, p-nitro-D-phenylalanine (p-nitro-D-Phe), 5,7-dichlorokynurenic acid (DCKA) and D-kyotorphin) and their L-Glu conjugates. DCKA was also conjugated with L-Asp and L-Gln amino acids. The analgesic activities of D-kyotorphin and its L-Glu conjugate were also evaluated. The results showed that the brain-to-plasma concentration ratio of D-MOD-L-Glu was higher than the D-MOD alone; however, the plasma concentration of both compounds were the same. The plasma concentration of p-nitro-D-Phe-L-Glu conjugate was higher than the parent p-nitro-D-Phe; however, the brain-to-plasma concentration ratio of p-nitro-D-Phe was higher than its conjugate. On the other hand, both DCKA and DCKA conjugates have a low brain-to-plasma concentration ratio due to their inability to cross the blood-brain barrier (BBB). The L-Asp and L-Glu conjugates of DCKA have elevated plasma concentrations relative to DCKA; however, the DCKA-L-Gln conjugate has the same plasma concentration as DCKA. For D-kyotorphin, both the parent and the L-Glu conjugate showed similar analgesic activity. In conclusion, conjugation of a non-permeable drug with L-Glu may improve the drug's brain delivery; however, this improvement may depend on the physicochemical and receptor binding properties of the conjugate.

High fever, renal failure, disseminated intravascular coagulation and myelodysplasia accompanied with enhanced angiogenesis possibly due to overexpression of vascular endothelial growth factor.

A 44-year-old woman suffered from recurrent fever, edema and fatigue. Laboratory data revealed renal dysfunction, low proteinemia, disseminated intravascular coagulation (DIC) and myelodysplasia. A renal and lymph node biopsy showed a marked angiogenesis. Serum levels of vascular endothelial growth factor (VEGF), and interleukin (IL)-6 were markedly increased, suggesting a pathogenesis related to VEGF-induced angiogenesis. The symptoms were remitted after treatment with cyclosporin A. No evidence of solid tumors, malignant lymphoma, Castleman's disease or POEMS (polyneuropathy, organomegaly, endocrine disorder, M-proteinemia and skin change) syndrome, reported to induce a high serum VEGF level, was obtained. This case may have involved an unknown mechanism which induced an overexpression of VEGF and IL-6.

Alpha1-adrenoceptors involvement in painful diabetic neuropathy: a role in allodynia.

To investigate whether alpha1-adrenoceptors are involved in pain behaviors in streptozotocin (STZ)-induced diabetic rats, we measured the effects of phenylephrine or prazosin on allodynia in the diabetic rats. Phenylephrine aggravated allodynia, while prazosin alleviated allodynia in the diabetic rats. We also measured alpha1-adrenoceptors gene expression or density of [3H]-prazosin binding sites in the dorsal root ganglia (DRG) and spinal cord in painful diabetic rats. Alpha1-adrenoceptors mRNA and density of [3H]prazosin binding sites were increased in the DRG of the diabetic rats, however there were no significant differences in alpha1-adrenoceptors expression in the spinal cord between the control and diabetic rats. These results suggest increased alpha1-adrenoceptors in the DRG may play a role in the pathogenesis of painful diabetic neuropathy.

Direct detection of apoptotic cells in peripheral blood from highly pathogenic SHIV-inoculated monkey.

Apoptosis in peripheral blood leukocytes (PBL) has been estimated by the enhancement of spontaneous apoptosis after in vitro culture, because apoptotic cells have not been observed directly in freshly isolated PBL in the course of HIV/AIDS. In monkeys infected with a highly pathogenic simian/human immunodeficiency virus (SHIV), which corresponds to rapid progressors of HIV infection, a high frequency of apoptotic cells was directly detected in fresh PBL by electron-microscopic studies. Peripheral blood apoptosis transiently occurred after intense plasma viremia, and peaking at 3 weeks postinfection; occurrence was not limited specifically to lymphocytes, but also occurred in other types of leukocytes. Apoptosis in peripheral lymph nodes was also detected following intense plasma viremia. However, the in vivo apoptosis was not detected in nonpathogenic SHIV-infected monkeys that showed no cell loss. Thus, we directly showed the apoptosis of PBL, which might be associated with pathogenic SHIV produced during the time of plasma viremia.

Left atrial systolic function assessed by left atrial ejection force in patients with sick sinus syndrome and paroxysmal atrial fibrillation.

We evaluated left atrial systolic function using left atrial ejection force (LAEF) in 19 patients with sick sinus syndrome (SSS) and in 20 with paroxysmal atrial fibrillation (Paf) whose ages ranged from 48 to 80 years. We also evaluated 35 normal individuals for comparison. The LAEF was calculated as 1/3 x mitral valve area x (peak velocity of A wave)2 using two-dimensional and pulsed-Doppler echocardiography according to Newton's law of motion and hydrodynamics. In normal individuals, LAEF positively correlated with age (r = 0.82, p < 0.01). Normal LAEF was calculated as 0.098 x age - 0.74 (kdynes) from the regression line. Because of this correlation, we used age-corrected LAEF (%LAEF) that was calculated as (measured LAEF / normal LAEF) x 100. The results showed that this value was 53+/-26% in patients with SSS and 54+/-26% in patients with Paf. Both were significantly lower than normal individuals (p < 0.001). Among SSS subtypes, %LAEF was lower in types II and III than in type I (51+/-14%, 37+/-19%, and 81+/-35%, respectively). In conclusion, left atrial systolic function is depressed in patients with Paf and SSS, in particular, types II and III. These results suggest that the pathological abnormalities extend not only to the sinus node but also to the left atrial muscle in patients with SSS and Paf.

Estimation of the systolic pulmonary arterial pressure using contrast-enhanced continuous-wave Doppler in patients with trivial tricuspid regurgitation.

Noninvasive estimation of pulmonary arterial pressure is important for hemodynamic monitoring of patients with heart disease. In patients with tricuspid regurgitation (TR), the peak velocity of TR on continuous-wave (CW) Doppler can be used to estimate the systolic pulmonary arterial pressure (PAPs) using the simplified Bernoulli equation. We evaluated a new technique of contrast-enhanced CW Doppler for calculating PAPs in patients with trivial TR. Forty-one patients without visible TR detected by color Doppler, pulsed Doppler or CW Doppler were evaluated. Age ranged from 19 to 73 (55 +/- 12) years old. Tricuspid flow signals were recorded on CW Doppler after intravenous administration of indocyanin green (ICG) or Albunex. PAPs was calculated as; PAPs = 4 x VTR2 + 10 mmHg, where VTR is the peak velocity of TR. PAPs calculated using contrast-enhanced CW Doppler was compared with PAPs measured by the following cardiac catheterization. 1) TR signals were recorded using the contrast-enhanced CW Doppler technique in 39 of 41 patients (95%) after intravenous administration of contrast agents. 2) The error of estimate of PAPs using the contrast-enhanced CW Doppler technique was -2.4 +/- 7.5 mmHg, and the percent error was -10.7 +/- 32.4% in all patients. In 20 of 39 patients (51%), the error of estimate was within +/- 5 mmHg. 3) PAPs was overestimated by 12.2 +/- 6.1 mmHg in patients with good contrast enhancement of TR signals. The contrast-enhanced CW Doppler technique is useful for estimating PAPs noninvasively in patients with trivial TR. It is better to assume the right atrial pressure as 3-5 mmHg, not 10 mmHg, in patients with good enhancement of trivial TR. Physiological TR may be enhanced by contrast agents in these patients.

Mental stress test is an effective inducer of vasospastic angina pectoris: comparison with cold pressor, hyperventilation and master two-step exercise test.

BACKGROUND: Cold pressor, hyperventilation and exercise stress tests were usually used for inducing an angina attack in patients with vasospastic angina pectoris. We induced vasospastic angina attack using the mental calculation stress test, and compared the results with those using other stress tests. SUBJECTS AND METHODS: Subjects were 29 patients with vasospastic angina pectoris. Their ages were 60.8+/-8.4 years. Coronary vasospasm was induced by an acetylcholine infusion test during coronary angiography. The mental stress test was performed as follows; after memorizing six digits numbers, they repeated these numbers in reverse for 5 min, and performed serial subtraction of 17 from 1000 for 5 min. Blood pressure, heart rate and ECG were recorded every 1-5 min during the mental stress test. The serum concentrations of epinephrine and norepinephrine were measured before and during the mental stress test. We compared these results with those obtained using cold pressor, hyperventilation and the Master two-step exercise stress test. RESULTS: (1) Eight of the 29 patients (28%) showed ischemic ST-T change, which was caused by the mental stress test. (2) The increase in norepinephrine was greater in patients with an ST-T change than without an ST-T change (0.11+/-0.06 vs. 0.04+/-0.04 ng/ml, P<0.01). (3) The incidence of the ST-T change caused by the mental stress test (28%) was similar to the cold pressor test (27%) and greater than that caused by the hyperventilation test (13%). The incidence of ST-T change caused by the Master two-step test was 55%. CONCLUSIONS: The mental stress test is an effective inducer of vasospastic angina attack, and attack may be induced by neurohumoral vasoconstrictive reflex and/or increased left ventricular afterload.